Leukotrienes are indicated as mediators of hyperoxia-inhibited alveolarization in newborn rats.

Abstract

We investigated the role of leukotrienes (LT) in hyperoxia-induced changes in lung parenchyma in neonatal rat pups. Rat pups were exposed to 21% O(2) (air) or >95% O(2) from days 4 to 14 after birth and were administered the 5-lipoxygenase (5-LO) inhibitor and LTD4 receptor antagonist Wy-50295, 5-LO-activating protein inhibitor MK-0591, or vehicle from days 3 to 14. All measurements were done on days 12-14. There was a significant (P < 0.05) increase in peptido-LT output from lung slices of animals exposed to O(2) compared with air-exposed animals. Both Wy-50295 and MK-0591 significantly lowered (P < 0.05) peptido-LT output in O(2)-exposed animals. The 6-ketoprostaglandin F(1alpha) output was increased similarly in both vehicle- and drug-treated O(2)-exposed animals. O(2) exposure also caused a significant increase in bronchoalveolar lavage fluid protein and extravascular lung water that could not be ameliorated by Wy-50295 or MK-0591. Hyperoxia-induced inhibition of alveolarization, indicated by a significantly (P < 0.05) lower parenchymal tissue density, specific internal surface area, and airspace perimeter-to-area ratio, and a significantly (P < 0.05) higher mean linear intercept and airspace unit volume than air-exposed animals, was prevented by both Wy-50295 and MK-0591. Although hyperoxia had no effect on septal thickness, Wy-50295 caused significant thickening in both air- and O(2)-exposed pups. Our studies provide evidence that hyperoxia-induced peptido-LT may mediate O(2)-induced inhibition of alveolarization and that this is not caused by an arachidonic acid shunt to cyclooxygenase.

• Authors: V Boros, J S Burghardt, C J Morgan, D M Olson
• Journal: The American journal of physiology (Am J Physiol) Vol. 272 Issue 3 Pt 1 Pg. L433-41 (Mar 1997) ISSN: 0002-9513 [Print] United States
• PMID: 9124600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Leukotrienes
• Lipoxygenase Inhibitors
• Naphthaleneacetic Acids
• Quinolines
• S(alpha)-methyl-6-(2-quinolinylmethoxy)-2-naphthaleneacetic acid
• MK 0591
• Arachidonate 5-Lipoxygenase

Topics

• Acute Disease
• Animals
• Animals, Newborn
• Arachidonate 5-Lipoxygenase
• Body Weight (drug effects)
• Female
• Hyperoxia (physiopathology)
• In Vitro Techniques
• Indoles (pharmacology)
• Leukotrienes (physiology)
• Lipoxygenase Inhibitors (pharmacology)
• Lung (growth & development)
• Lung Injury
• Male
• Naphthaleneacetic Acids (pharmacology)
• Pulmonary Alveoli (cytology, drug effects)
• Quinolines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Time Factors